Stability of inbred mouse strain differences in behavior and brain size between laboratories and across decades

Abstract

If we conduct the same experiment in two laboratories or repeat a classical study many years later, will we obtain the same results? Recent research with mice in neural and behavioral genetics yielded different results in different laboratories for certain phenotypes, and these findings suggested to some researchers that behavior may be too unstable for fine-scale genetic analysis. Here we expand the range of data on this question to additional laboratories and phenotypes, and, for the first time in this field, we formally compare recent data with experiments conducted 30 -50 years ago. For ethanol preference and locomotor activity, strain differences have been highly stable over a period of 40 -50 years, and most strain correlations are in the range of r ‫؍‬ 0.85-0.98, as high as or higher than for brain weight. For anxiety-related behavior on the elevated plus maze, on the other hand, strain means often differ dramatically across laboratories or even when the same laboratory is moved to another site within a university. When a wide range of phenotypes is considered, no inbred strain appears to be exceptionally stable or labile across laboratories in any general sense, and there is no tendency to observe higher correlations among studies done more recently. Phenotypic drift over decades for most of the behaviors examined appears to be minimal.agonistic behavior ͉ anxiety ͉ ethanol preference ͉ gene-environment interaction ͉ locomotor activity

Ethanol Withdrawal-Associated Drinking and Drinking in the Dark: Common and Discrete Genetic Contributions

“…Across the 3 available data sets [4,21,22], the strain mean correlation between g/kg intake and preference ratio (the proportion of total daily fluid ingested from the ethanol bottle) was r = 0.88 across these 41 strains. Since we believe g/kg intake to be the superior index of avidity for ethanol solutions (as it depends less on the concentration of ethanol offered than does the preference ratio), we correlated the g/kg intake from the two-bottle tests with g/kg intake from the DID test, as well as the BEC after DID.…”

“…On the other hand, we had previously compared S13 HDID-1 and G64 HS mice for two bottle preference drinking using a protocol very similar to those employed for the inbred strain studies [4,21,22]. In that comparison, strains were offered 4 days each of choice between 3%, 6%, 9%, 12%, 15% ethanol versus water, and then higher concentrations [14].…”

“…Belknap [22] used the same increasing series of ethanol concentrations but for only 3 days at each concentration in a test of 15 inbred strains aged 9-11 weeks. Bachmanov [4] tested 28 strains aged about 8 weeks for 4 days of 10% ethanol vs water.…”

“…Genetic contributions to individual differences in this two-bottle preference assay were noted in rats in the 1940's [1] and across inbred mouse strains in the 1950's [2]. Ethanol preference (the proportion of total daily fluid taken from the ethanol-containing bottle) is a trait with relatively high heritability [3] and surveys of multiple inbred mouse strains have shown that strains' characteristic ethanol preference is highly stable genetically across 50 years and multiple laboratories [4]. …”

Voluntary ethanol consumption in 22 inbred mouse strains

“…Thus, another advantage to inbred strain studies is that testing multiple strains that exhibit a range of behavioral responses will allow estimation of genetic correlations. For example, recent work documented that preference for a 10% ethanol solution is highly stable over a period of 40-50 years, with most strain correlations across studies in the range of 0.89 -0.98 (Wahlsten et al, 2006). (n.b., this comparison included some of the 10% ethanol preference data reported in the current manuscript).…”